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Microbial polysaccharide, HS-142-1, competitively and selectively inhibits ANP binding to its guanylyl cyclase-containing receptor.

During the search for ANP receptor ligands of microbial origin, we isolated a novel polysaccharide, HS-142-1, from culture broth of Aureobasidium sp. HS-142-1 inhibited [125I]-rANP binding to ANP receptor in rabbit kidney cortex membranes with an IC50 of 0.3 mu g/ml, but gave no effects on specific binding of [125I]-Endothelin nor [125I]-Angiotensin II to their respective receptors in bovine lung membranes. HS-142-1 competitively and selectively inhibited ANP binding to its guanylyl cyclase-containing receptor purified from solubilized bovine adrenocortical membranes and blocked cGMP production elicited by ANP. HS-142-1 is the first non-peptide antagonist selective for ANP functional receptor and will be a powerful tool to elucidate the physiological functions of ANP.

Adrenal Cortex↗

ZILA-SRM: a probabilistic framework with zero-inflated latent models for robust strain reconstruction from metagenomes.

UNLABELLED: Resolving bacterial strain diversity from shotgun metagenomic data is fundamental to understanding intra-host evolution, transmission dynamics, and phenotypic heterogeneity. However, current probabilistic approaches face a severe "identifiability limit" when disentangling highly similar genomes. Under high-noise conditions, sequencing errors, coverage overdispersion, and collinearity confound standard expectation-maximization algorithms, resulting in overfitting and spurious "ghost" strains. Here, we introduce zero-inflated latent allocation for strain reconstruction from metagenomes with adaptive sparsity regularization (ZILA-SRM) to overcome this barrier through three innovations. First, we integrate a zero-inflated Poisson mixture model to decouple "structural zeros" (true strain absence) from "sampling zeros" (stochastic dropout), addressing overdispersion in standard Poisson-based tools. Second, we impose a convex adaptive sparsity regularization penalty that leverages biological sparsity priors to shrink noise artifacts dynamically. Third, we implement a graph-theoretic refinement step using maximal clique enumeration to resolve haplotype collinearity. Benchmarking against StrainFinder and MixtureS on 702 synthetic data sets shows that ZILA-SRM achieves a 20% improvement in precision in high-complexity scenarios while maintaining over 80% recall for minor variants at 0.5% abundance. Re-analysis of deep-sequencing data from 195 Mycobacterium tuberculosis clinical samples reveals cryptic low-abundance drug-resistant variants in 12% of patients, including a minor clone carrying the rpoB S450L mutation. Furthermore, application to skin microbiome data sets further reveals a strong negative correlation between dominant Staphylococcus aureus and Staphylococcus epidermidis strains, providing genomic evidence for competitive exclusion. These findings establish ZILA-SRM as a robust tool for resolving strain-level diversity in complex metagenomes. IMPORTANCE: Understanding microbial communities at the strain level is critical because closely related strains can differ dramatically in traits such as drug resistance, virulence, and ecological interactions. However, resolving individual strains from metagenomic sequencing data remains difficult, especially when strains are highly similar or present at low abundance. As a result, biologically meaningful diversity is often obscured or misinterpreted as noise. In this study, we introduce a new framework that improves the reliability of strain reconstruction from complex metagenomic data. By reducing false-positive strain detection while preserving sensitivity to rare variants, our approach enables more accurate characterization of microbial populations. This improved resolution reveals previously hidden subpopulations in clinical and microbiome datasets, providing clearer insights into microbial evolution, competition, and the emergence of clinically relevant traits such as antibiotic resistance.

Metagenomics↗

ADSA Foundation Scholar Award: defining dairy flavors.

Production and consumption of dairy foods continue to increase annually. Further, new ingredient applications for dairy foods continue to expand. With continued production and consumption, there is also increased competition. Increased competition exists regionally, nationally, and globally. Processors as well as product developers must find ways to maximize existing markets and expand into new markets. A consistent high quality product is necessary to maintain competitiveness. Although microbial safety and stability are key ways to define quality, flavor is one method of defining quality that is often assumed or overlooked. The aggressive and competitive nature of today's market demands more precise and powerful tools for defining flavor and flavor quality. Traditional as well as more recent methods for evaluating dairy flavor are reviewed. The application of defining sensory flavors to fundamental research on flavor chemistry, product understanding, and effective marketing is addressed.

Animals↗

Iron acquisition in microbial pathogenesis.

Successful competition for iron by potential pathogens is essential to establish infection. The roles of the various types of microbial iron acquisition systems in host-pathogen interactions depend on the nature of the infection and the location of the pathogen within the host. Microbes infecting the extracellular spaces of the host employ different strategies for iron acquisition than those that invade and multiply within host cells.

Animals↗

Overuse of high stability antibiotics and its consequences in public and environmental health.

In this paper the ecological aspects of widespread antibiotic consumption are described. Many practitioners, veterinarians, breeders, farmers and analysts work on the assumption that a antibiotics undergo spontaneous degradation. It is well documented that the indiscriminate use of antibiotics has led to the water contamination, selection and dissemination of antibiotic-resistant organisms, alteration of fragile ecology of the microbial ecosystems. The damages caused by the overuse of antibiotics include hospital, waterborne and foodborne infections by resistant bacteria, enteropathy (irritable bowel syndrome, antibiotic-associated diarrhea etc.), drug hypersensitivity, biosphere alteration, human and animal growth promotion, destruction of fragile interspecific competition in microbial ecosystems etc. The consequences of heavy antibiotic use for public and environmental health are difficult to assess: utilization of antibiotics from the environment and reduction of irrational use is the highest priority issue. This purpose may be accomplished by bioremediation, use of probenecid for antibiotic dosage reduction and by adoption of hospital infections methodology for control resistance in natural ecosystems.

Agriculture↗

Selection for plasmid post-segregational killing depends on multiple infection: evidence for the selection of more virulent parasites through parasite-level competition.

Is the virulence of parasites an outcome of optimized infection? Virulence has often been considered an inevitable consequence of parasite reproduction when the cost incurred by the parasite in reducing the fitness of its current host is offset by increased infection of new hosts. More recent models have focused on how competition occurring between parasites during co-infection might effect selection of virulence. For example, if co-infection was common, parasites with higher intrinsic growth rates might be selected, even at the expense of being optimally adapted to infect new hosts. If growth rate is positively correlated with virulence, then competition would select increased virulence. We tested these models using a plasmid-encoded virulence determinant. The virulence determinant did not contribute to the plasmid's reproduction within or between hosts. Despite this, virulent plasmids were more successful than avirulent derivatives during selection in an environment allowing within-host competition. To explain these findings we propose and test a model in which virulent parasites are selected by reducing the reproduction of competitors.

Animals↗

Possible implications of biocide accumulation in the environment on the prevalence of bacterial antibiotic resistance.

The lethality of biocides depends upon their interaction with a number of distinct biochemical targets. This often reflects reactive chemistry for any given agent, such as thiol oxidation. Susceptibility may vary markedly between different target organisms, and changes within the more sensitive targets can alter the inhibitory effect. The multiplicity of potential targets, however, usually dictates against the development of overt resistance to concentrations used for hygienic applications. Similarly, although changes in cellular permeability toward such agents, mediated either by envelope modification or the induction of efflux-pumps may reduce susceptibility, they rarely influence the outcome of treatments at use-concentration. It has recently been proposed that chronic exposure of the environment to biocides used in a variety of commercial products might expose some microbial communities to subeffective concentrations causing emergence of resistant clones. Such resistance might relate to mutational changes in the most susceptible target or to regulatory mutants that cause the constitutive expression of certain efflux pumps. Although selection of organisms with such modifications is unlikely to influence the effectiveness of the biocides, changes in their susceptibility to third-party antibiotics can be postulated. This is particularly the case where a cellular target is shared between a biocide and an antibiotic, or where induction of efflux is sufficient to confer antibiotic resistance in the clinic. Although such linkage has been demonstrated in the laboratory in pure culture, it has not been documented in environments commonly exposed to biocides. In nature, the effects of chronic stressing with biocides are complicated by competition between microbial community members that may result in clonal expansion of naturally insusceptible clones.

Anti-Bacterial Agents↗

The Gfr Uptake System Provides a Context-Dependent Fitness Advantage to Salmonella Typhimurium SL1344 During the Initial Gut Colonization Phase.

Salmonella enterica serovar Typhimurium (S. Tm) is a major cause of foodborne diarrhea. However, in healthy individuals, the microbiota typically restricts the growth of incoming pathogens, a protective mechanism termed colonization resistance (CR). To circumvent CR, Salmonella strains can utilize private nutrients that remain untapped by the resident microbiota. However, the metabolic pathways and environmental niches promoting pathogen growth are still not completely understood. Here, we investigate the significance of the gfr operon in gut colonization of S. Tm, which is essential for the utilization of fructoselysine (FL) and glucoselysine (GL). These Amadori compounds are present in heated foods with high protein and carbohydrate contents. We detected FL in both mouse chow and the intestinal tract of mice and showed that gfr mutants are attenuated during the initial phase of colonization in the murine model. Experiments in gnotobiotic mice and competition experiments with Escherichia coli suggest that gfr-dependent fitness advantage is context-dependent. We conclude that dietary Amadori products like FL can support S. Tm gut colonization, depending on the metabolic capacities of the microbiota.

Salmonella typhimurium↗

Computational mass spectrometry and genome mining guided discovery of metallophores produced by Microbulbifer.

Iron is an essential component of cellular biology. Thus, iron's low bioavailability is a key evolutionary pressure guiding microbial dynamics in the marine environment. Among marine bacteria, Microbulbifer is a chemically underexplored and functionally versatile bacterial genus, which is commonly associated with sponges, algae, corals, and sediments. Previously, genome analyses have revealed that Microbulbifer spp. can degrade polymers and synthesize natural products. Despite their recognized potential to produce secondary metabolites, siderophores are yet to be identified in Microbulbifer, and their iron acquisition strategies remain largely unknown. Here, we developed a comprehensive mass spectrometry-based query language code to determine siderophore production by Microbulbifer spp. in mono- and mixed cultures. Using this workflow, we discovered a new metallophore, which we named bulbichelin, as well as a suite of previously unreported petrobactins containing an unprecedented longer chain length acylation on the central spermidine moiety. We applied genome mining methods to describe the biosynthesis of these compounds. Using metal infusion mass spectrometry, we show that bulbichelins bind a variety of metals. Notably, neither of these compounds were produced in a co-culture of Microbulbifer with coral-derived pathogen Vibrio coralliilyticus Cn52-H1. Understanding how siderophores shape interspecies interactions between Microbulbifer spp. and other marine organisms will aid in unraveling the chemical and catalytic versatility of this genus and adaptation in nutrient deplete marine environment.

MassQL↗

Modeling and biological implication of time-dose-mortality data for the entomophthoralean fungus, zoophthora anhuiensis, on the green peach aphid myzus persicae

The entomophthoralean fungus Zoophthora anhuiensis frequently causes epizootics in populations of the green peach aphid, Myzus persicae, infesting cruciferous crops in the middle and lower regions of the Changjiang River, China, during late autumn and early winter. In this study, a bioassay was conducted by exposing aphids on detached leaves to varying doses of Z. anhuiensis conidia discharged from in vitro cultures. Ten doses (1.5-198 conidia/mm2) were used, with each dose including 64-120 aphids. The aphids were maintained at 18 degreesC under a photophase of 12:12 (L:D) and observed daily for mortality. The resulting time-dose-mortality data fitted well to a conditional mortality probability model based on the Hosmer-Lemeshow test (C = 9.52, df = 8, P = 0.70), resulting in a cumulative mortality probability model. The parameters from the latter model were used to estimate the lethal dose (LD50) and time (LT50) for the fungal species against the pest. The LD50 values were 87, 44, and 34 conidia/mm2 on days 5, 6, and 7 after exposure, respectively. The estimates of the LT50 values decreased from 6.7 days at 37 conidia/mm2 to 4.5 days at 198 conidia/mm2. The results indicate that Z. anhuiensis could be a promising aphid pathogen for microbial control competitive with other Zoophthora species. The model is recommended for use in the analysis of time-dose-mortality data for fungus-insect associations. The biological implications of the parameters and the advantages of the modeling technique over the conventional method of probit analysis are discussed. Copyright 1998 Academic Press.

Journal Article↗

Growth kinetics and competition--some contemporary comments.

Results of competition experiments with one growth-limiting factor under idealized experimental conditions have been reported extensively, and usually provide ample support for the conclusion that 'complete competitors cannot coexist'. However, under conditions of multiple substrate limitation and discontinuous or alternating supply of nutrients, coexistence of species is quite common. Since such patterns of nutrient supply may be expected to prevail in many natural environments the mechanisms ruling the survival and growth of bacteria under such conditions need to be understood. However, it appears that surprisingly little is known of the physiological state of individual competing species grown in mixed cultures. Unfortunately, basic information such as the actual concentration of limiting nutrients is lacking in most cases. But perhaps the recent development of new and powerful techniques to explore the physiological properties even of individual cells will further stimulate studies into the mechanisms behind the competitiveness of microbial species.

Bacteria↗

Mechanism of inactivation of a Fasciola proteolytic enzyme by peptide aldehydes and alkylating agents.

A proteolytic enzyme of the liver fluke Fasciola sp. was purified as described previously by ammonium sulfate fractionation, gel filtration on Sephadex G-200 column and L-phenylalanine-agarose chromatography. Leupeptin, a peptide aldehyde of microbial origin, competitively inhibited the enzyme activity with respect to the substrate alpha-N-benzoyl-L-argininamide; the apparent Ki value for leupeptin is 45 000-fold less than the apparent Km for the substrate. Incubation of the enzyme with leupeptin resulted in time-dependent inactivation of the globinolytic activity, with an inactivation constant (Kinact) of 0.4 microM giving the half-maximum inactivation velocity, and with a minimum inactivation half-time (T) of 2.7 min at infinite concentration of this compound. The inactivated enzyme was not reactivated by extensive dialysis. These results imply that leupeptin yields an affinity labelling of an active site of the enzyme. The activity of the Fasciola proteolytic enzyme was also inactivated by other peptide aldehydes and alkylating agents and inactivation constants observed were 0.5 microM for chymostatin, 13 microM for antipain, 2 microM for p-toluenesulfonyl-L-lysine chloromethyl ketone, 140 microM for p-toluenesulfonyl-L-phenylalanine chloromethyl ketone and 40 microM for iodoacetate under the conditions used.

Aldehydes↗

A comparative study of sulfidogenic and methanogenic activities during the treatment of landfill leachate: part I.

A comprehensive anaerobic leachate treatment in batch reactors was conducted for 9 months. Activities of two main bacterial groups, sulfidogens and methanogens were observed with monitoring parameters as chemical oxygen demand (COD), total gas production, pH, alkalinity, dissolved sulfide and volatile suspended solids/total suspended solids (VSS/TSS). Leachate contained high concentrations of volatile fatty acids. Some competition between microbial species was observed. COD was applied at a range of 1100-8200 mg/L at a slowly increasing rate over time. COD removal was mostly above 80%, dissolved sulfide was produced at a range of 100-450 mg/L in the first weeks, proving high sulfidogenic activity and making 40-50% of COD removal. Methanogenesis seemed under stress and improved after several weeks with increasing COD load whereas hydrogen sulfide (HS-) production leveled off around 100 mg/L, making 4-8% COD removal by sulfidogens. Then, 40-70% of overall COD removal was achieved by methanogens. Volatile fatty acids (VFA) except acetic acid (propionic, isobutyric, butyric, isovaleric, valeric, caproic and heptanoic acids) were readily degraded and found near detection limit on gas chromatographic runs, accordingly VFA-oxidizing bacteria were assumed to be highly active and tolerant to sulfide levels encountered in our study, also with hydrogenotrophic groups providing favorable conditions for the process. pH was the key parameter to determine the degree of inhibition from sulfurous species. Alkalinity was produced proportionally with COD applied as a result of VFA degradation. Overall system performance was good and optimum pH was 7.8-8.2 at which inhibition due to unionized VFA was eliminated.

Anaerobiosis↗

Effects of amendment with ferrihydrite and gypsum on the structure and activity of methanogenic populations in rice field soil.

Methane emission from paddy fields may be reduced by the addition of electron acceptors to stimulate microbial populations competitive to methanogens. We have studied the effects of ferrihydrite and gypsum (CaSO(4). 2H(2)O) amendment on methanogenesis and population dynamics of methanogens after flooding of Italian rice field soil slurries. Changes in methanogen community structure were followed by archaeal small subunit (SSU) ribosomal DNA (rDNA)- and rRNA-based terminal restriction fragment length polymorphism analysis and by quantitative SSU rRNA hybridization probing. Under ferrihydrite amendment, acetate was consumed efficiently (<60 microM) and a rapid but incomplete inhibition of methanogenesis occurred after 3 days. In contrast to unamended controls, the dynamics of Methanosarcina populations were largely suppressed as indicated by rDNA and rRNA analysis. However, the low acetate availability was still sufficient for activation of Methanosaeta spp., as indicated by a strong increase of SSU rRNA but not of relative rDNA frequencies. Unexpectedly, rRNA amounts of the novel rice cluster I (RC-I) methanogens increased significantly, while methanogenesis was low, which may be indicative of transient energy conservation coupled to Fe(III) reduction by these methanogens. Under gypsum addition, hydrogen was rapidly consumed to low levels ( approximately 0.4 Pa), indicating the presence of a competitive population of hydrogenotrophic sulfate-reducing bacteria (SRB). This was paralleled by a suppressed activity of the hydrogenotrophic RC-I methanogens as indicated by the lowest SSU rRNA quantities detected in all experiments. Full inhibition of methanogenesis only became apparent when acetate was depleted to nonpermissive thresholds (<5 microM) after 10 days. Apparently, a competitive, acetotrophic population of SRB was not present initially, and hence, acetotrophic methanosarcinal populations were less suppressed than under ferrihydrite amendment. In conclusion, although methane production was inhibited effectively under both mitigation regimens, different methanogenic populations were either suppressed or stimulated, which demonstrates that functionally similar disturbances of an ecosystem may result in distinct responses of the populations involved.

Calcium Sulfate↗

Escherichia coli: on-farm contamination of animals.

Escherichia coli is one of the main inhabitants of the intestinal tract of most mammalian species, including humans, and birds. Shiga toxin-producing E. coli (STEC), also called verotoxinogenic E. coli, usually do not cause disease in animals but may cause watery diarrhoea, haemorrhagic colitis, and/or haemolytic uraemic syndrome in humans. Zoonotic STEC include the O157:H7 strains and, with increasing frequency, certain non-O157 strains. The importance of non-O157 zoonotic strains is probably underestimated as they have been less well characterised and are more difficult to detect in samples than O157:H7. Another large subset of STEC strains has been isolated from animals but has not, at the present time, been associated with disease in animals or humans. Cattle and other ruminants are the most important reservoir of zoonotic STEC, which are transmitted to humans through the ingestion of foods or water contaminated with animal faeces, or through direct contact with the infected animals or their environment. The main sources of STEC infection of cattle on-farm are the drinking water, the feed, and the immediate environment of the animal. Risk factors that have been identified for infection of animals with O157 STEC include age, weaning, movement of the animals, season, feed composition, and the ability of the bacteria to persist in the environment. On-farm control of the zoonotic risk of human infection with STEC should primarily target the main source of contamination: the animal reservoir. Various strategies to reduce intestinal colonisation of cattle by zoonotic STEC have been tried with varying results, including vaccination, treatment with probiotics, such as direct-fed microbials or competitive exclusion, administration of bacteriophages, and modification of the diet.

Animal Husbandry↗

[Peptide inhibitors of a bacterial collagenase].

The properties of the cleavage site of collagen by collagenases remain discussed. The authors report their studies on the active site of the collagenase of a bacteria, achromobacter, based on two types of methods. The first type uses synthetic substrates, the second one enzymatic inhibitors. The results of both methods are reviewed. The inhibitors seem more sensitive than substrates to study the relation between structure and activity of the enzyme.

Alcaligenes↗

Viral and microbial genotyping by a combination of multiplex competitive hybridization and specific extension followed by hybridization to generic tag arrays.

Detection and identification of microbial pathogens are important for disease diagnosis, treatment and prophylaxis measurements. By introducing an innovative technique, we show a robust, reliable and accurate microarray-based method for identification of microbial pathogens. The technique utilizes a unique combination of multiplex competitive hybridization, which enhances hybridization accuracy of oligonucleotides to the specific target, and apyrase-mediated allele-specific extension, which improves specific extension. As a model system, different clinically relevant human papillomaviruses were selected for this study. The method generated accurate results and proves to be promising for specific and correct microbial and viral typing.

DNA Primers↗

The growth of pure and simple microbial competitors in a moving distributed medium.

The dynamics of pure and simple competition between two microbial species are examined for the case of interaction arising in a distributed and nonstagnant environment. The environment is modeled as a tubular reactor. It is shown that for relatively small values of the dispersion coefficient (i.e., for small, but nonzero, backmixing of the medium), the two competing populations can coexist in a stable steady state. It has been assumed that the species grow uninhibited and that if there are maintenance requirements they are satisfied from endogenous sources. From numerical studies it has been found that a necessary condition for coexistence is that the net specific growth rate curves of the two competitors cross each other at a positive value of the concentration of the rate-limiting substrate. The model equations have been numerically solved by using the methods of orthogonal and spline collocation.

Animals↗